Antibody-Mediated Rejection of the Lung in Patients with Short Telomeres

Abstract

PurposeShort telomeres are associated with interstitial lung disease (ILD) and immune dysregulation. Prior studies have suggested that lung transplant recipients with short telomeres experience high rates of renal dysfunction, cytopenias, and infections and may have reduced survival and time to onset of chronic lung allograft dysfunction. It is unknown whether immune dysfunction related to short telomeres contributes to post-transplant complications such as antibody-mediated rejection (AMR). We investigated whether leukocyte telomere length (LTL) is a risk factor for developing AMR.MethodsThis is a single-center retrospective cohort study of 114 ILD patients who underwent lung transplantation between January 1, 2008 and December 31, 2017. Pre-transplant leukocyte telomere length (LTL) was measured using qPCR. Age-adjusted telomere length was calculated by comparing against a reference population, and dichotomized above and below the 10th percentile. Each patient underwent serial testing for donor-specific antibodies (DSA) and transbronchial biopsies per institutional protocol. AMR was graded according to the 2016 ISHLT consensus report and graded as definite and probable AMR. The acute cellular rejection (ACR) score was computed as the sum of the total numeric Grade A ACR in the follow up period. Multivariable logistic regression was used to assess potential predictors of AMR and included age, sex, ACR score, transplant type and LTL as covariates.ResultsThere were 35 (30.7%) patients with age-adjusted LTL < 10th percentile. DSA was positive in 67 (58.8%) patients. Definite and probable AMR occurred in 11 (9.6%) and 16 patients (14.0%), respectively. Development of AMR was not associated with LTL < 10th percentile (p=0.274). After adjustment, LTL < 10th percentile does not increase the odds of AMR (OR 0.70; 95% CI, 0.24-2.04; P=0.516). However, ACR score was associated with AMR (OR 1.25; 95% CI 1.04-1.51; P=0.020).ConclusionPre-transplant LTL < 10th percentile does not appear to be a risk factor for development of AMR. Short telomeres are associated with interstitial lung disease (ILD) and immune dysregulation. Prior studies have suggested that lung transplant recipients with short telomeres experience high rates of renal dysfunction, cytopenias, and infections and may have reduced survival and time to onset of chronic lung allograft dysfunction. It is unknown whether immune dysfunction related to short telomeres contributes to post-transplant complications such as antibody-mediated rejection (AMR). We investigated whether leukocyte telomere length (LTL) is a risk factor for developing AMR. This is a single-center retrospective cohort study of 114 ILD patients who underwent lung transplantation between January 1, 2008 and December 31, 2017. Pre-transplant leukocyte telomere length (LTL) was measured using qPCR. Age-adjusted telomere length was calculated by comparing against a reference population, and dichotomized above and below the 10th percentile. Each patient underwent serial testing for donor-specific antibodies (DSA) and transbronchial biopsies per institutional protocol. AMR was graded according to the 2016 ISHLT consensus report and graded as definite and probable AMR. The acute cellular rejection (ACR) score was computed as the sum of the total numeric Grade A ACR in the follow up period. Multivariable logistic regression was used to assess potential predictors of AMR and included age, sex, ACR score, transplant type and LTL as covariates. There were 35 (30.7%) patients with age-adjusted LTL < 10th percentile. DSA was positive in 67 (58.8%) patients. Definite and probable AMR occurred in 11 (9.6%) and 16 patients (14.0%), respectively. Development of AMR was not associated with LTL < 10th percentile (p=0.274). After adjustment, LTL < 10th percentile does not increase the odds of AMR (OR 0.70; 95% CI, 0.24-2.04; P=0.516). However, ACR score was associated with AMR (OR 1.25; 95% CI 1.04-1.51; P=0.020). Pre-transplant LTL < 10th percentile does not appear to be a risk factor for development of AMR.